Bacteria-Cell Interactions - INSERM U604 and INRA USC2020  


  HEADProf. Pascale Cossart / pascale.cossart@pasteur.fr
  MEMBERSHead of the unit: COSSART Pascale Professor IP – classe exceptionnelle
Researchers : BIERNE Hélène Dr, Directrice de Recherche (DR2) INRA - PhD / DUSSURGET Olivier Dr, Chargé de Recherche IP - PhD / HAMON Mélanie Dr, Assistante de Recherche IP - PhD / LEBRETON Alice Dr, Chargée de Recherche (CR2) INRA - PhD / PIZARRO-CERDA Javier Dr, Chargé de Recherche IP - PhD
Engineers : GOUIN Edith Ingénieur de recherche IP / NAHORI Marie-Anne Ingénieur de recherche IP / THAM To Nam Ingénieur de recherché IP
Technician : VILLIERS Véronique Technicienne IP
Secretariat : BAUDIER Martine Post-doctoral members: ARCHAMBAUD Cristel PhD / BALESTRINO Damien PhD / BONAZZI Matteo PhD / BRUCK Serawit PhD / MOSTOWY Serge PhD / RIBET David PhD / STAVRU Fabrizia PhD / TOLEDO Alejandro PhD / VEIGA Esteban PhD PhD students : AUBRY Camille / DORTET Laurent / PERSONNIC Nicolas / SESTO Nina Trainees : GUET-REVILLET Hélène Master 2 student


  Annual Report

Our research focuses on the analysis of the infectious process by intracellular bacteria, using as a model system Listeria monocytogenes. Our goal is to identify bacterial and cellular components - and of course the mechanisms in which they are involved - which are critical for establishment and persistence of a Listeria infection. We use multidisciplinary approaches ranging from post-genomics to cell biology approaches in particular in vivo imaging and relevant animal models to ultimately unravel at the molecular level the pathophysiology of human listeriosis. Our studies on Listeria shed light on events occuring at the cell and tissue levels as well as at the level of the whole animal, and contribute to generate new concepts in infection biology and in fundamental cell biology.

Non coding RNAs and novel RNA-mediated regulations : We had identified nine small RNAs, generated a program to predict targets and validated targets for three of them. We now focus on one of them which is not present in the non pathogenic species L. innocua, displays a series of repeats and is involved in virulence by a so far unknown mechanism. We have also generated whole genome tiling arrays and study the transcriptome of a Listeria wild type strain and of several mutants after growth in various conditions. This has allowed to establish the first bacterial operon map, to identify 50 non-coding RNAs and several unexpected transcripts which could play critical roles in regulation.

New virulence factors: We concentrate our efforts on several surface and secreted proteins. We have identified a novel protein of the internalin family, InlJ whose role in virulence is clearly established but which does not play any role during infection of cultured cells. This protein is under a post transcriptional regulation and is only expressed in animals after several days of infection. Its function is so far unknown. We are addressing the role of a secreted protein of the internalin family which is highly produced inside the cytosol of infected cells. Finally, we have identified a secreted protein which goes to the cell nucleus. Experiments indicate an interaction with a protein which has a role in heterochromatin formation and in the epigenetic control of gene expression during infection.

The cell biology of the invasion process: We have extended our finding that the clathrin-mediated endocytosis machinery is used during Listeria InlB mediated entry, to the internalin pathway and also to other zipering bacteria. We have discovered successive post-translational modifications of E-cadherin during infection (phosphorylation and ubiquitination) and the involvement of both caveolin and clathrin in the initial steps of the infectious process, Together these data highligh novel similarities between Listeria entry and adherens junction formation. In addition, we have discovered that septins which are increasingly recognized as novel cytoskeleton elements are controling the entry of Listeria and other bacteria. A role for septin in pathogen internalization had never been reported.

Crossing of the placental barrier. Our long term project -with Marc Lecuit now responsible for a G5 entitled (Microorganisms and host barriers)- aiming at identifying the bacterial strategies used to cross the materno fetal barrier was reached using a natural host for Listeria, the gerbil and a new animal model, i.e. a knock-in humanized E-cadherin mouse line. These studies demonstrated that both internalin and InlB are required for entry into the syncitiotrophoblast cell layer and the fetal infection. It is the first time that such a detailed analysis of a materno fetal infection is reported.

Keywords: Endocytosis, bacterial invasion, post-translational modifications, RNAs, host barriers



  Publications

S. Sousa, D. Cabanes, F. Colland, M. Lecuit, P. Legrain and P. Cossart. (2005)ARHGAP10 is necessary for -catenin recruitment at adherens junctions and for Listeriainvasion. Nat. Cell Biol., 7 : 954-960.

E.Veiga and P. Cossart. (2005) Listeriahijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat. Cell. Biol., 7 : 894-900.

M.A. Hamon, E. Batsché, B. Régnault, T.N. Tham, S. Seveau, C. Muchardt and P. Cossart.(2007) Histone modifications induced by a family of bacterial toxins. Proc Natl Acad SciU S A., 104: 13467-72. Erratum in: Proc Natl Acad Sci U S A., 104: 17555.

E. Veiga, J. A. Guttman, M. Bonazzi, E. Boucrot, A. Toledo-Arana, A. E. Lin, J. Enninga, J. Pizarro-Cerda, B. B. Finlay, T. Kirchhausen, and P. Cossart (2007). Invasive and adherent bacterial pathogens co-Opt host clathrin for infection. Cell Host Microbe, 2:340-51.

O. Disson, S. Grayo , E. Huillet, G. Nikitas, F. Langa-Vives, O. Dussurget, M. Ragon, A. Le Monnier, C. Babinet, P. Cossart and M. Lecuit(2008.) Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature, 455(7216):1114-8.



  Web Site

More informations on our web site




Activity Reports 2009 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr